Colorectal cancer (CRC) causes 655,000 deaths worldwide per year and is the third most common cancer in the United States. Patients with late-stage CRC have limited treatment options and molecular therapies are highly desired. The epidermal growth factor receptor (EGFR) plays a growth-promoting role in many types of cancer. Inhibition of EGFR signals by EGFR blocking antibodies and by EGFR kinase inhibitors is a successful molecular therapy for lung cancer patients. Despite widespread expression of EGFR in CRC, clinical trials with anti-EGFR therapy have been largely disappointing for CRC. Patients with mutations in KRAS have not responded well in these trials. Moreover, stratification of CRC patients based on the presence or absence of KRAS mutations has not been an effective or sensitive prognostic or predictive method.
In clinical trials of panitumumab (Vectibix®) and cetuximab (Erbitux®), patients with KRASmut tumors did not benefit from these drugs. However, other studies have shown that a subpopulation of CRC patients with KRASmut tumors do respond to anti-EGFR therapies. Thus, KRASwt and KRASmut status alone are not effective indicators of anti-EGFR response.